DESCRIPTION: The research in this proposal is designed to provide a fundamental understanding of the influence of various types of paint product formulations on the dermatopharmacokinetics of two commonly encountered solvents, toluene and methyl ethyl ketone (MEK). This research will enhance the ability to accurately extrapolate animal studies to relevant human exposure scenarios and improve hazard and risk assessments. Experimental studies will be conducted with rats using a novel real-time breath analysis system coupled with physiologically based pharmacokinetic (PBPK) modeling to determine the penetration rate of toluene and MEK through the skin. The resultant data from these comprehensive evaluations are directly applicable to regulatory agencies in establishing dermal absorption guidelines that mimic actual occupational exposure situations. The specific research objectives are: (1) to describe dermal absorption of toluene and MEK using PBPK models in order to determine skin permeability constants; (2) to evaluate the kinetics and dermal bioavailability of exposure to aqueous and MEK; (3) to describe the dose-dependent kinetics of exposure to toluene and MEK in characterized paint products; and (4) to compare different paint product formulations on the percutaneous absorption of toluene and MEK.